Multigene panel testing for hereditary breast and/or ovarian cancer risk assessment is likely to result in altered screening and prevention recommendations for a substantial number of patients

medwireNews: The results of multigene panel testing for hereditary breast and ovarian cancer mutations other than those in BRCA1 or BRCA2 could alter the clinical management of not only the tested individuals, but also their family members, study findings indicate.

“Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes”, Leif Ellisen, from Massachusetts General Hospital Cancer Center in Boston, USA, and fellow investigators write in JAMA Oncology.

Their study included 1046 participants negative for BRCA1 and BRCA2 mutations who were referred for genetic counselling, genetic testing or both for hereditary breast and/or ovarian cancer risk assessment.

Multigene testing using either a 29- or 25-gene panel showed that 3.8% of participants harboured mutations in other genes known to be associated with predisposition to hereditary cancers, a prevalence that is consistent with previous reports, say the researchers.

Of the 41 mutations detected in 40 participants, the majority (n=26) were in genes associated with a low-to-moderate risk of hereditary breast and/or ovarian cancer, three were in high-risk breast cancer genes, eight in genes associated with Lynch syndrome and four in genes linked to other cancers.

A further 23 participants known to be positive for mutations in genes other than BRCA1 or BRCA2 were also recruited for the clinical management analysis.

When assessing all 63 mutation-positive cases, over 90% were shown to have mutations in genes consistent with the personal or family history, “suggesting that these mutations are clinically significant for these individuals”, say the researchers.

And indeed, applying gene-specific National Comprehensive Cancer Network (NCCN) guidelines in the context of personal and/or family history, they found that the clinical management of 56% of mutation-positive patients would change on the basis of the multigene test findings, including recommendations for additional screening and/or prevention strategies.

Moreover, the test results would result in recommendations for additional genetic testing in 72% of 58 first-degree family members.

In a related commentary, Elizabeth Swisher, from University of Washington Medical Center in Seattle, USA, explains that with the rising use of multigene testing, it is important to assess the clinical utility of such testing.

She applauds the study authors for “tackling this important and challenging question”, and points out that although actionability is a critical reason for considering genetic testing, defining the term is not easy.

“The authors use NCCN guidelines as a standardized measure, but the NCCN recommendations are incomplete for many genes”, she writes.

The commentator adds: “Actionability may also be undervalued by only assessing the effect of identifying damaging mutations. This approach assigns no utility to negative findings, which can also lead to changes in clinical care and improved risk assessment.”